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Study Liver Cytochrome P450 3A4 Inhibition and Hepatotoxicity Using DMSO-Differentiated HuH-7 Cells

  • Yitong LiuEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1473)

Abstract

Metabolically competent, inexpensive, and robust in vitro cell models are needed for studying liver drug-metabolizing enzymes and hepatotoxicity. Human hepatoma HuH-7 cells develop into a differentiated in vitro model resembling primary human hepatocytes after a 2-week dimethyl sulfoxide (DMSO) treatment. DMSO-treated HuH-7 cells express elevated cytochrome P450 3A4 (CYP3A4) enzyme gene expression and activity compared to untreated HuH-7 cells. This cell model could be used to study CYP3A4 inhibition by reversible and time-dependent inhibitors, including drugs, food-related substances, and environmental chemicals. The DMSO-treated HuH-7 model is also a suitable tool for investigating hepatotoxicity. This chapter describes a detailed methodology for developing DMSO-treated HuH-7 cells, which are subsequently used for CYP3A4 inhibition and hepatotoxicity studies.

Key words

HuH-7 DMSO CYP3A4 Inhibition Hepatotoxicity 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Applied ToxicologyOffice of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug AdministrationLaurelUSA

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